Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematop...Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.展开更多
We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic ste...We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We identified the prognostic factors of disease-free survival(DFS)in a training subset(n=593),then assigned a weighted score using these factors to the remaining patients(validation subset;n=296).The multivariable model identified two independent predictors of DFS:DRI and HCT-CI before transplantation.In this scoring system,we assigned a weighted score of 2 to very high-risk DRI,and assigned a weighted score of 1 to high-risk DRI and intermediate-and high-risk HCT-CI(i.e.,haplo-DRCI).In the validation cohort,the three-year DFS rate was 65.2%(95%confidence interval(CI),58.2%–72.2%),55.8%(95%CI,44.9%–66.7%),and 32.0%(95%CI,5.8%–58.2%)for the low-,intermediate-,and high-risk group,respectively(P=0.005).Haplo-DRCI can also predict DFS in disease-specific subgroups,particularly in acute leukemia patients.Increasing score was also significantly predictive of increased relapse,increased non-relapse mortality(NRM),decreased DFS,and decreased overall survival(OS)in an independent historical cohort(n=526).These data confirmed that haplo-DRCI could effectively risk stratify haplo-HSCT recipients and provide a tool to better predict who will best benefit from haplo-HSCT.展开更多
Allogeneic hematopoietic stem cell transplant(HSCT) remains the only potentially curative option for variety of hematologic disorders. Lack of a suitable fully HLAmatched donor limits this option for many patients. Wi...Allogeneic hematopoietic stem cell transplant(HSCT) remains the only potentially curative option for variety of hematologic disorders. Lack of a suitable fully HLAmatched donor limits this option for many patients. Without a suitable related or unrelated HLA-matched donor,umbilical cord blood and haploidentical family members provide a potential source of stem cells. Timely donor availability makes haploidentical donors an attractive alternative donor source. Initial attempts at haploidentical HSCT was associated with significantly increased mortality owing to high rates of graft rejection and severe graftversus-host disease caused by major donor-recipient HLAdisparity. However, over the past decade, outcomes of haploidentical HSCT have improved significantly. Here, we review the advantages and challenges of haploidentical transplantation. We also discuss new developments to attempt to overcome the challenges to a successful haploidentical transplantation.展开更多
BACKGROUND With the rapid development of haploidentical hematopoietic stem cell transplantation(haplo-HSCT),primary poor graft function(PGF)has become a lifethreatening complication.Effective therapies for PGF are inc...BACKGROUND With the rapid development of haploidentical hematopoietic stem cell transplantation(haplo-HSCT),primary poor graft function(PGF)has become a lifethreatening complication.Effective therapies for PGF are inconclusive.New Chinese patent medicine Pai-Neng-Da(PND)Capsule exerts dual effect in promoting hematopoiesis recovery and regulating immunity.Still,the application of PND capsule in hematopoietic stem cell transplantation,especially in the haplo-HSCT setting,has not yet been reported.AIM To evaluate the role of PND capsule in acute leukemia patients with haplo-HSCT.METHODS We retrospectively collected data of acute leukemia patients who underwent haplo-HSCT at the Affiliated People’s Hospital of Ningbo University between April 1,2015 and June 30,2020.Twenty-nine consecutive patients received oral PND capsule from the sixth day to the first month after haplo-HSCT were included in the PND group.In addition,31 patients who did not receive PND capsule during haplo-HSCT were included in the non-PND group.Subsequently,we compared the therapeutic efficacy according to the western medical evaluation indexes and Chinese medical symptom scores,and the survival between the PND group and the non-PND group,using the chi-square test,Fisher’s exact test,and the Kaplan-Meier method.RESULTS The duration of platelet engraftment was shorter in the PND group than in the non-PND group(P=0.039).The PND group received a lower frequency of red blood cells and platelet transfusions than the non-PND group(P=0.033 and P=0.035,respectively).In addition,PND capsule marginally reduced the rate of PGF(P=0.027)and relapse(P=0.043).After 33(range,4-106)months of follow-up,the 3-year relapse-free survival(P=0.046)and progression-free survival(P=0.049)were improved in the PND group than in the non-PND group.Also,the therapeutic efficacy of the PND group according to Chinese medical symptom scores was significantly better than that of the non-PND group(P=0.022).Moreover,the adverse events caused by PND capsule were mild.Nevertheless,there were no significant differences in the duration of neutrophil engraftment,the risk of infection within 100 days after haplo-HSCT,the acute graft-versus-host disease,or the 3-year overall survival between the two groups.CONCLUSION PND capsule could promote hematopoiesis reconstitution,improve the therapeutic efficacy of Chinese medical symptom scores,present anti-tumor effectiveness,and prolong the survival of acute leukemia patients with haplo-HSCT.展开更多
THYMOMA, a relatively rare epithelial neoplasm with unique clinical and pathologic features, is the most usual diagnosis for a mass located in the mediastinum. It is often associated withautoimmune disorders. The myas...THYMOMA, a relatively rare epithelial neoplasm with unique clinical and pathologic features, is the most usual diagnosis for a mass located in the mediastinum. It is often associated withautoimmune disorders. The myastnema gravls ano pure red cell aplasia are the most common disorders, with the incidences of 40% and 5%, respectively, while the incidence of aplastic anemia is only about 0-1.4%. 1 Thymectomy is hard to perform on patients with severe aplastic anemia（SAA） due to severe pancytopenia.展开更多
Here we report a successful protocol in treatment of a patient with primary plasma cell leukemia (PPCL) using haploidentical stem cell transplantation (hi-HSCT). During first complete remission after routine chemother...Here we report a successful protocol in treatment of a patient with primary plasma cell leukemia (PPCL) using haploidentical stem cell transplantation (hi-HSCT). During first complete remission after routine chemotherapy, the patient received autologous blood stem cell transplantation, but he had relapse later. He gained a second CR after chemotherapy and underwent hi-HSCT from his daughter, who had HLA mismatched at three loci. Recovery of hemopoiesis was found at day 14 and complete donor chimerism was confirmed by PCR-STR on day 34, 95 and 238. The patients have survived disease-free for 56 months since hi-HSCT, without serious graft-versus-host-disease.展开更多
To study the effect of natural killer （NK） cells on graft-versus-host disease （GVHD） after H-2 haploidentical bone marrow transplantation （BMT） in mice. Methods ：Murine model of H-2 haploidentical BMT was estab...To study the effect of natural killer （NK） cells on graft-versus-host disease （GVHD） after H-2 haploidentical bone marrow transplantation （BMT） in mice. Methods ：Murine model of H-2 haploidentical BMT was established by using Balb/c （H- 2d） mouse as recipient, and Balb/c （H-2d）×C57BL/6 （H-2b） （H-2db） mouse as donor. Lethally irradiated Balb/c （H-2d） mice were transplanted with the bone marrow cells from Balb/c（H-2d）×C57BL/6（H-2b） （H-2db） mice containing donor spleen cells and/or NK cells. GVHD and survival rates were studied by observation of clinical manifestations and pathological changes. Results：In the group of bone marrow ＋spleen cells, GVHD was induced in 90% mice; but in the group plus with low amount of NK cells, GVHD was induced in 20% mice; and in the group transplanted with high amount of NK cells, GVHD was induced only in 10% mice. Compared to the group transplanted only with BM plus spleen cells, the incidences of GVHD in the latter two groups decreased significantly （P 〈 0.01） and the survival rates at different periods of 15, 30, 45 and 60 days increased obviously （P 〈 0.01）. Conclusion： In mouse H-2 haploidentical BMT, alloreactive NK cells can reduce the incidence of GVHD and increase the survival rate.展开更多
BACKGROUND Haploidentical hematopoietic stem cell transplantation(Haplo-HSCT)is often performed in children with hematologic malignancies.Faced with the gap in the literature regarding the approach to experiences rela...BACKGROUND Haploidentical hematopoietic stem cell transplantation(Haplo-HSCT)is often performed in children with hematologic malignancies.Faced with the gap in the literature regarding the approach to experiences related to Haplo-HSCT with pediatric patients with leukemias and myelodysplasias aged up to 18 years,there was an interest in exploring the clinical outcomes of patients undergoing this treatment.AIM To identify and summarize the scientific contributions available on Haplo-HSCT performed in the last 10 years in children and adolescents with myeloid and lymphoid leukemias and myelodysplasias,aged up to 18 years.METHODS This is a descriptive systematic review.We extracted data including characteristics of participants,health condition,characteristics of the donation,conditioning regimen,recurrent clinical complications and clinical outcomes.The Virtual Health Library Brazil,PubMed,EMBASE,and SciELO platforms were used,finding a total of 1052 studies.After the eligibility criteria and complete reading of the texts,18 articles were included for analysis.RESULTS The total sample of all study cohorts was 1825 patients,mostly male,the highest reported median age was 15.0 years and the lowest was 1.2 years.Acute graftversus-host disease and chronic graft-versus-host disease were observed in almost all studies.Relapse,graft rejection and delayed immune recovery were identified as major clinical challenges.Pre-transplant minimal positive residual disease was identified in 288 patients.Infections are also among the main clinical complications,viral,bacterial and fungal infections being reported.It is observed that in the 5-year interval,the lowest rates of EFS and overall survival(OS)were 29.5%and 68.0%,respectively.While,the highest rates of EFS and OS,in the same interval,were 80.1%and 81.0%.CONCLUSION Haplo-HSCT represents a promising therapy,considering the potential number of possible donors and the conditioning and treatment platforms that can be offered.The results obtained show that this type of transplant has a strong antileukemic effect,with generally favorable OS rates.Overcoming relapse as the first cause of transplant failure is the great clinical challenge.展开更多
Objective To evaluate the efficacy of rituximab-containing regimens on post - transplantation lympho-proliferative disorder ( PTLD ) following haploidentical hematopoietic stem cell transplantation ( HSCT) . Methods T...Objective To evaluate the efficacy of rituximab-containing regimens on post - transplantation lympho-proliferative disorder ( PTLD ) following haploidentical hematopoietic stem cell transplantation ( HSCT) . Methods The clinical data of 3 cases of PTLD after haploidentical HSCT were analyzed retrospectively. Time展开更多
Objective To investigate the therapeutic effects of haploidentical hematopoietic stem - cell transplantation ( Haplo - PBSCT) for acute myeloid leukemia in first relapse after complete remission by standard induction ...Objective To investigate the therapeutic effects of haploidentical hematopoietic stem - cell transplantation ( Haplo - PBSCT) for acute myeloid leukemia in first relapse after complete remission by standard induction chemotherapy. Methods Eighty - nine cases of AML in first relapse after complete remission by standard DA展开更多
To the Editor:Thalassemia major(TM)is a prevalent public health issue in southern China,necessitating allogeneic hematopoietic stem cell transplantation(allo-HSCT)as a curative treatment.Only a small proportion of TM ...To the Editor:Thalassemia major(TM)is a prevalent public health issue in southern China,necessitating allogeneic hematopoietic stem cell transplantation(allo-HSCT)as a curative treatment.Only a small proportion of TM patients have a sibling identical donor(SID),therefore alternative donors,including human leukocyte antigen(HLA)matched unrelated donors(MUDs)and haploidentical donors(HIDs),are increasingly being adopted by transplant centers.Several centers have indicated that MUD transplantation does not differ from SID transplantation in terms of overall survival(OS)or event-free survival(EFS)in recent years,although early complications such as graft versus host disease(GVHD)are more common among MUD transplantation.展开更多
Objective To investigate the association between earlyimmune reconstitution and Epstein-Barrrvirus(EBV)reactivation by analyzing changes in natural killer(NK),B,and T cells and their functional status in the periphera...Objective To investigate the association between earlyimmune reconstitution and Epstein-Barrrvirus(EBV)reactivation by analyzing changes in natural killer(NK),B,and T cells and their functional status in the peripheral blood during the early post-transplant period.Methods This study included 23 patients who underwent haplo-hematopoietic stem cell transplantation(HSCT).The immune reconstitution of NK cells,T cells,and B cells as well as the expression levels of NK and T cell exhaustion markers(PD-1,TIM-3,and CTLA-4)and cytotoxic function at 1,2,and 3 months post-transplantation were compared between patients with EBV activation(EBV+group)and those without activation(EBV-group)post-transplantation.Results EBV activation occurredinninepatients posttransplantation(EBV+group),whereas 14 patients demonstrated no activation(EBV-group).All patients with EBV activation exhibited EBV viremia,and no EBV-associateddiseasesoccurred.No significant differences in the clinical characteristicswereffound between the two ggroupsof patients.The median proportion of CD3^(+)CD8^(+)T cells in the EBV+group was significantly lower than that in the EBV-group at 1 month post-transplantation(P=0.033).The median proportion of the CD3^(-)CD16^(neg)CD56^(bri)subset in the EBV+group was significantly higher than that in the EBV-group at 2 months postransplantation(P=0.046).No significant differences in the median proportions of CD3^(-)CD19^(+)B cells were observed between the two groups at 1,2,and 3 months post-transplantation.The expression of CTLA-4 on CD3^(-)CD16^(bri)CD56^(dim)NK cells in the EBV+group was significantly higher than that in the EBV-group at 1 month post-transplantation(P=0.033).The expression of TIM-3 on CD3^(+)CD8^(+)T cells in the EBV+group was significantly higher than that in the EBV-group(P=0.009).The expression level of TIM-3 on CD3^(-)CD16^(neg)CD56^(dim)NK cells in the EBV+group was significantly lower than that in the EBV-group at 2 months post-transplantation(P=0.023).The expression levels of TIM-3 on CD3^(+)CD4^(+)T cells in the EBV+group than those in the EBV-group at 1 and 3 months post-transplantation(P=0.002,P=0.043).The median positive rate of Granzyme B expression in CD3^(+)CD8^(+)T cells and CD3^(+)CD4^(+)T cells in the EBV+group was significantly lower than that in the EBV-group at 1-month post-transplantation(P=0.033,P=0.016).The median positive rate of Granzyme B expression in the CD3^(-)CD16^(bri)CD56^(neg)cell subset in the EBV+group was higher than that in the EBV-group at 2 months post-transplantation(P=0.012).The median positive rate of Granzyme B expression in CD3^(+)CD4^(+)T cells in the EBV+group remained significantly lower than that in the EBV-ggroup at 2 months posttransplantation(P=0.049).The median positive rate of perforin expression in the CD3^(-)CD16^(bri)CD56^(dim)cell subset was significantly higher in the EBV+group than in the EBV-group at 3 months post-transplantation(P=0.003).The median positive rate of IFNexpression in CD3^(+)CD8^(+)T cells in the EBV+group was significantly lower than that in the EBV-group at 3 months post-transplantation(P=0.036).Conclusion Delayed NK cell and T lymphocyte reconstitution,high exhaustion marker expression,and weakened cytotoxic functions may be related to EBV reactivation after haploidentical HSCT.展开更多
To the Editor:Patients with relapsed or refractory(R/R)acute lymphoblastic leukemia(ALL)have a poor prognosis,with a 5-year overall survival(OS)ranging from 25%to 50%,and remission induction therapy is challenging.[1]...To the Editor:Patients with relapsed or refractory(R/R)acute lymphoblastic leukemia(ALL)have a poor prognosis,with a 5-year overall survival(OS)ranging from 25%to 50%,and remission induction therapy is challenging.[1]Allogeneic hematopoietic stem cell transplantation(HSCT)is the golden standard treatment for patients with R/R ALL.Before immunotherapy was introduced into clinical practice,a significant proportion of patients could not undergo HSCT because of serious adverse events from chemotherapy or the inability to achieve an acceptably deep remission.展开更多
With the advances in allogeneic hematopoietic cell transplantation(allo-HCT)and supportive care,the number of allo-HCT for elderly patients has been increasing in recent years.However,the advanced donor age limits the...With the advances in allogeneic hematopoietic cell transplantation(allo-HCT)and supportive care,the number of allo-HCT for elderly patients has been increasing in recent years.However,the advanced donor age limits the availability of human leukocyte antigen(HLA)-matched sibling donors(MSD)for elderly individuals.展开更多
We aimed to identify dynamic changes of lysine(K)-specific methyltransferase 2A partial tandem duplications(KMT2A-PTD)before and after haploidentical donor hematopoietic stem cell transplantation(HID HSCT)and explore ...We aimed to identify dynamic changes of lysine(K)-specific methyltransferase 2A partial tandem duplications(KMT2A-PTD)before and after haploidentical donor hematopoietic stem cell transplantation(HID HSCT)and explore the prognostic value of pre-transplantation levels of KMT2A-PTD in acute myeloid leukemia(AML)receiving HID HSCT.Consecutive 64 AML patients with KMT2A-PTD positivity at diagnosis receiving HID HSCT were included in this study.Patients with KMT2A-PTD≥1%before HSCT had a slower decrease of KMT2A-PTD after HID HSCT.Patients with KMT2A-PTD≥1%before HID HSCT had a higher cumulative incidence of relapse(36.4%,95%confidence interval[CI]:6.3%-66.5%)at 2 years after HSCT than those with KMT2A-PTD<1%(7.5%,95%CI:0.3%-14.7%,P=.010).In multivariable analysis,KMT2A-PTD≥1%before HID HSCT was the only independent risk factor for relapse(hazard ratio[HR]:4.90;95%CI:1.22-19.59;P=.025).Thus,pre-transplantation levels of KMT2A-PTD could predict relapse in AML patients following HID HSCT.展开更多
Since 1968 when the first successful hematopoietic stem cell transplantation(HSCT) was performed, transplant technique has developed rapidly for more than 50 years. In the past 20 years, the significant breakthroughs ...Since 1968 when the first successful hematopoietic stem cell transplantation(HSCT) was performed, transplant technique has developed rapidly for more than 50 years. In the past 20 years, the significant breakthroughs and widely use of haploidentical-related donor HSCT(e.g. Beijing Protocol) make everyone can have a donor(1), and the novel, reduced-toxicity transplant regimens help elderly patients receive HSCT safely(2).展开更多
Human leukocyte antigen (HLA)-matched donors for hematopoietic stem cell transplantation (HSCT) have long been scarce in China. Haploidentical (haplo) donors are available for the vast majority of patients, but toxici...Human leukocyte antigen (HLA)-matched donors for hematopoietic stem cell transplantation (HSCT) have long been scarce in China. Haploidentical (haplo) donors are available for the vast majority of patients, but toxicity has limited this approach. Three new approaches for haplo-HSCT originated from Italy, China, and USA in 1990 and have been developed to world-renowned system up to now. The Chinese approach have been greatly improved by implementing new individualized conditioning regimens, donor selection based on non-HLA systems, risk-directed strategies for graft-versus-host disease and relapse, and infection management. Haplo-HSCT has exhibited similar efficacy to HLA-matched HSCT and has gradually become the predominant donor source and the first alternative donor choice for allo-HSCT in China. Registry-based analyses and multicenter studies adhering to international standards facilitated the transformation of the unique Chinese experience into an inspiration for the refinement of global practice.This review will focus on how the new era in which "everyone has a donor" will become a reality in China.展开更多
Given that randomized studies testing the long-term impact of antithymocyte globulin(ATG)dosing are scarce,we report the results of an extended follow-up from the original trial.In our prospective,multicenter,randomiz...Given that randomized studies testing the long-term impact of antithymocyte globulin(ATG)dosing are scarce,we report the results of an extended follow-up from the original trial.In our prospective,multicenter,randomized trial,408 leukemia patients 14–65 years of age who underwent haploidentical hematopoietic cell transplantation(haplo-HCT)under our original“Beijing Protocol”were randomly assigned one-to-one to ATG doses of 7.5 mg/kg(n=203,ATG-7.5)or 10 mg/kg(n=205,ATG-10.0)at four sites.Extended follow-up(median 1968 d(range:1300–2710 d)indicated comparable 5-year probabilities of moderate-to-severe chronic graft-versus-host disease(GVHD)(hazard ratio(HR):1.384,95%confidence interval(CI):0.876–2.189,P=0.164),nonrelapse mortality(HR:0.814,95%CI:0.526–1.261,P=0.357),relapse(HR:1.521,95%CI:0.919–2.518,P=0.103),disease-free survival(HR:1.074,95%CI:0.783–1.473,P=0.658),and GVHD-free/relapse-free survival(HR:1.186,95%CI:0.904–1.555,P=0.219)between groups(ATG-7.5 vs.ATG-10.0).The 5-year rate of late effects did not differ significantly.However,the cytomegalovirus/Epstein-Barr virus-related death rate was much higher in the ATG-10.0 cohort than in the ATG-7.5 cohort(9.8%vs.1.5%;P=0.003).In summary,patients undergoing haplo-HCT benefit from 7.5 mg/kg ATG compared to 10.0 mg/kg ATG based on a balance between GVHD and infection control.ATG(7.5 mg/kg)is potentially regarded as the standard regimen in the platform.These results support the optimization of ATG use in the“Beijing Protocol”,especially considering the potential economic advantage in developing countries.展开更多
In recent decades,haploidentical stem cell transplantation(haplo-SCT)to treat severe aplastic anemia(SAA)has achieved remarkable progress.However,long-term results are still lacking.We conducted a multicenter prospect...In recent decades,haploidentical stem cell transplantation(haplo-SCT)to treat severe aplastic anemia(SAA)has achieved remarkable progress.However,long-term results are still lacking.We conducted a multicenter prospective study involving SAA patients who underwent haplo-SCT as salvage therapy.Long-term outcomes were assessed,mainly focusing on survival and quality of life(QoL).Longitudinal QoL was prospectively evaluated during pretransplantation and at 3 and 5 years posttransplantation using the SF-36 scale in adults and the PedsQL 4.0 scale in children.A total of 287 SAA patients were enrolled,and the median follow-up was 4.56 years(range,3.01–9.05 years)among surviving patients.During the long-term follow-up,268 of 275 evaluable patients(97.5%)obtained sustained full donor chimerism,and 93.4%had complete hematopoietic recovery.The estimated overall survival and failure-free survival for the whole cohort at 9 years were 85.4%±2.1%and 84.0%±2.2%,respectively.Age(≥18 years)and a poorer performance status(ECOG>1)were identified as risk factors for survival outcomes.For Qo L recovery after haplo-SCT,we found that QoL progressively improved from pretransplantation to the 3-year and 5-year time points with statistical significance.The occurrence of chronic graft versus host disease was a risk factor predicting poorer QoL scores in both the child and adult cohorts.At the last followup,74.0%of children and 72.9%of adults returned to normal school or work.These inspiring long-term outcomes suggest that salvage transplantation with haploidentical donors can be routine practice for SAA patients without human leukocyte antigen(HLA)-matched donors.展开更多
A key issue in the haploiedntical hematopoietic stem cell transplantation(haplo-HSCT) setting is the search for the best donor, because donor selection can significantly impact the clinical outcomes. We aimed to ident...A key issue in the haploiedntical hematopoietic stem cell transplantation(haplo-HSCT) setting is the search for the best donor, because donor selection can significantly impact the clinical outcomes. We aimed to identify the role of collateral related donors(CRDs) in donor selection for haplo-HSCT through comparing the clinical outcomes between CRDs(n = 60) and maternal donors(MDs, n = 296), which were the last choice of donor selection in immediate related donors(IRDs). The cumulative incidence of graft-versus-host disease was comparable between CRDs and MDs. The 5-year cumulative incidence of relapse and non-relapse mortality was 22.0%(95% CI, 11.3%–32.7%) versus 17.4%(95% CI, 13.0%–21.8%)(P = 0.455) and 25.0%(95% CI, 13.9%–36.1%) versus 23.1%(95% CI, 18.2%–28.0%)(P = 0.721) for the CRDs and MDs, respectively. The 5-year probabilities of disease-free survival and overall survival was 53.2%(95% CI, 40.4%–66.0%) versus 59.5%(95% CI, 53.8%–65.2%)(P = 0.406) and 56.5%(95% CI,43.8%–69.2%) versus 61.8%(95% CI, 56.1%–67.5%)(P = 0.458) for the CRDs and MDs, respectively.Female donor/male recipient(FDMR) CRDs were associated with the poorest clinical outcomes, and the clinical outcomes of non-FDMR CRDs were comparable to those of MDs. In summary, our results showed that CRDs did not showed superiority over MDs. Thus, IRDs should be the first choice of donor selection, and CRDs could only be the donors for those without IRDs.展开更多
基金supported by the Key Program of the National Natural Science Foundation of China(No.81930004)the National Natural Science Foundation of China(No.82170208)+2 种基金Tongzhou District Distinguished Young Scholars(No.JCQN2023009)Plan Project of Tongzhou Municipal Science and Technology(No.KJ2024CX045)Beijing Natural Science Foundation(No.Z230016)。
文摘Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.
基金This work was supported by the National Key Research and Development Program of China(2017YFA0104500)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)+6 种基金the Key Program of the National Natural Science Foundation of China(81930004)Capital’s Funds for Health Improvement and Research(2018-4-4089)CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-034)the Science and Technology Project of Guangdong Province of China(2016B030230003)the Project of Health Collaborative Innovation of Guangzhou City(201704020214)Peking University Clinical Scientist Program(BMU2019LCKXJ003)supported by the Fundamental Research Funds for the Central Universities.
文摘We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We identified the prognostic factors of disease-free survival(DFS)in a training subset(n=593),then assigned a weighted score using these factors to the remaining patients(validation subset;n=296).The multivariable model identified two independent predictors of DFS:DRI and HCT-CI before transplantation.In this scoring system,we assigned a weighted score of 2 to very high-risk DRI,and assigned a weighted score of 1 to high-risk DRI and intermediate-and high-risk HCT-CI(i.e.,haplo-DRCI).In the validation cohort,the three-year DFS rate was 65.2%(95%confidence interval(CI),58.2%–72.2%),55.8%(95%CI,44.9%–66.7%),and 32.0%(95%CI,5.8%–58.2%)for the low-,intermediate-,and high-risk group,respectively(P=0.005).Haplo-DRCI can also predict DFS in disease-specific subgroups,particularly in acute leukemia patients.Increasing score was also significantly predictive of increased relapse,increased non-relapse mortality(NRM),decreased DFS,and decreased overall survival(OS)in an independent historical cohort(n=526).These data confirmed that haplo-DRCI could effectively risk stratify haplo-HSCT recipients and provide a tool to better predict who will best benefit from haplo-HSCT.
文摘Allogeneic hematopoietic stem cell transplant(HSCT) remains the only potentially curative option for variety of hematologic disorders. Lack of a suitable fully HLAmatched donor limits this option for many patients. Without a suitable related or unrelated HLA-matched donor,umbilical cord blood and haploidentical family members provide a potential source of stem cells. Timely donor availability makes haploidentical donors an attractive alternative donor source. Initial attempts at haploidentical HSCT was associated with significantly increased mortality owing to high rates of graft rejection and severe graftversus-host disease caused by major donor-recipient HLAdisparity. However, over the past decade, outcomes of haploidentical HSCT have improved significantly. Here, we review the advantages and challenges of haploidentical transplantation. We also discuss new developments to attempt to overcome the challenges to a successful haploidentical transplantation.
基金Supported by The Zhejiang Provincial Science and Technology Program of Traditional Chinese Medicine,No.2017ZA129 and No.2018ZA112.
文摘BACKGROUND With the rapid development of haploidentical hematopoietic stem cell transplantation(haplo-HSCT),primary poor graft function(PGF)has become a lifethreatening complication.Effective therapies for PGF are inconclusive.New Chinese patent medicine Pai-Neng-Da(PND)Capsule exerts dual effect in promoting hematopoiesis recovery and regulating immunity.Still,the application of PND capsule in hematopoietic stem cell transplantation,especially in the haplo-HSCT setting,has not yet been reported.AIM To evaluate the role of PND capsule in acute leukemia patients with haplo-HSCT.METHODS We retrospectively collected data of acute leukemia patients who underwent haplo-HSCT at the Affiliated People’s Hospital of Ningbo University between April 1,2015 and June 30,2020.Twenty-nine consecutive patients received oral PND capsule from the sixth day to the first month after haplo-HSCT were included in the PND group.In addition,31 patients who did not receive PND capsule during haplo-HSCT were included in the non-PND group.Subsequently,we compared the therapeutic efficacy according to the western medical evaluation indexes and Chinese medical symptom scores,and the survival between the PND group and the non-PND group,using the chi-square test,Fisher’s exact test,and the Kaplan-Meier method.RESULTS The duration of platelet engraftment was shorter in the PND group than in the non-PND group(P=0.039).The PND group received a lower frequency of red blood cells and platelet transfusions than the non-PND group(P=0.033 and P=0.035,respectively).In addition,PND capsule marginally reduced the rate of PGF(P=0.027)and relapse(P=0.043).After 33(range,4-106)months of follow-up,the 3-year relapse-free survival(P=0.046)and progression-free survival(P=0.049)were improved in the PND group than in the non-PND group.Also,the therapeutic efficacy of the PND group according to Chinese medical symptom scores was significantly better than that of the non-PND group(P=0.022).Moreover,the adverse events caused by PND capsule were mild.Nevertheless,there were no significant differences in the duration of neutrophil engraftment,the risk of infection within 100 days after haplo-HSCT,the acute graft-versus-host disease,or the 3-year overall survival between the two groups.CONCLUSION PND capsule could promote hematopoiesis reconstitution,improve the therapeutic efficacy of Chinese medical symptom scores,present anti-tumor effectiveness,and prolong the survival of acute leukemia patients with haplo-HSCT.
基金Supported by the Key Provincial Talents Program of Jiangsu Province(H201126)the Natural Science Fund for Colleges and Universities of Jiangsu Province(09KJB320015)+1 种基金Key Projects in the National Science&Technology Pillar Program(2008BAI61B02 and 2008ZX09312-026)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘THYMOMA, a relatively rare epithelial neoplasm with unique clinical and pathologic features, is the most usual diagnosis for a mass located in the mediastinum. It is often associated withautoimmune disorders. The myastnema gravls ano pure red cell aplasia are the most common disorders, with the incidences of 40% and 5%, respectively, while the incidence of aplastic anemia is only about 0-1.4%. 1 Thymectomy is hard to perform on patients with severe aplastic anemia（SAA） due to severe pancytopenia.
文摘Here we report a successful protocol in treatment of a patient with primary plasma cell leukemia (PPCL) using haploidentical stem cell transplantation (hi-HSCT). During first complete remission after routine chemotherapy, the patient received autologous blood stem cell transplantation, but he had relapse later. He gained a second CR after chemotherapy and underwent hi-HSCT from his daughter, who had HLA mismatched at three loci. Recovery of hemopoiesis was found at day 14 and complete donor chimerism was confirmed by PCR-STR on day 34, 95 and 238. The patients have survived disease-free for 56 months since hi-HSCT, without serious graft-versus-host-disease.
文摘To study the effect of natural killer （NK） cells on graft-versus-host disease （GVHD） after H-2 haploidentical bone marrow transplantation （BMT） in mice. Methods ：Murine model of H-2 haploidentical BMT was established by using Balb/c （H- 2d） mouse as recipient, and Balb/c （H-2d）×C57BL/6 （H-2b） （H-2db） mouse as donor. Lethally irradiated Balb/c （H-2d） mice were transplanted with the bone marrow cells from Balb/c（H-2d）×C57BL/6（H-2b） （H-2db） mice containing donor spleen cells and/or NK cells. GVHD and survival rates were studied by observation of clinical manifestations and pathological changes. Results：In the group of bone marrow ＋spleen cells, GVHD was induced in 90% mice; but in the group plus with low amount of NK cells, GVHD was induced in 20% mice; and in the group transplanted with high amount of NK cells, GVHD was induced only in 10% mice. Compared to the group transplanted only with BM plus spleen cells, the incidences of GVHD in the latter two groups decreased significantly （P 〈 0.01） and the survival rates at different periods of 15, 30, 45 and 60 days increased obviously （P 〈 0.01）. Conclusion： In mouse H-2 haploidentical BMT, alloreactive NK cells can reduce the incidence of GVHD and increase the survival rate.
文摘BACKGROUND Haploidentical hematopoietic stem cell transplantation(Haplo-HSCT)is often performed in children with hematologic malignancies.Faced with the gap in the literature regarding the approach to experiences related to Haplo-HSCT with pediatric patients with leukemias and myelodysplasias aged up to 18 years,there was an interest in exploring the clinical outcomes of patients undergoing this treatment.AIM To identify and summarize the scientific contributions available on Haplo-HSCT performed in the last 10 years in children and adolescents with myeloid and lymphoid leukemias and myelodysplasias,aged up to 18 years.METHODS This is a descriptive systematic review.We extracted data including characteristics of participants,health condition,characteristics of the donation,conditioning regimen,recurrent clinical complications and clinical outcomes.The Virtual Health Library Brazil,PubMed,EMBASE,and SciELO platforms were used,finding a total of 1052 studies.After the eligibility criteria and complete reading of the texts,18 articles were included for analysis.RESULTS The total sample of all study cohorts was 1825 patients,mostly male,the highest reported median age was 15.0 years and the lowest was 1.2 years.Acute graftversus-host disease and chronic graft-versus-host disease were observed in almost all studies.Relapse,graft rejection and delayed immune recovery were identified as major clinical challenges.Pre-transplant minimal positive residual disease was identified in 288 patients.Infections are also among the main clinical complications,viral,bacterial and fungal infections being reported.It is observed that in the 5-year interval,the lowest rates of EFS and overall survival(OS)were 29.5%and 68.0%,respectively.While,the highest rates of EFS and OS,in the same interval,were 80.1%and 81.0%.CONCLUSION Haplo-HSCT represents a promising therapy,considering the potential number of possible donors and the conditioning and treatment platforms that can be offered.The results obtained show that this type of transplant has a strong antileukemic effect,with generally favorable OS rates.Overcoming relapse as the first cause of transplant failure is the great clinical challenge.
文摘Objective To evaluate the efficacy of rituximab-containing regimens on post - transplantation lympho-proliferative disorder ( PTLD ) following haploidentical hematopoietic stem cell transplantation ( HSCT) . Methods The clinical data of 3 cases of PTLD after haploidentical HSCT were analyzed retrospectively. Time
文摘Objective To investigate the therapeutic effects of haploidentical hematopoietic stem - cell transplantation ( Haplo - PBSCT) for acute myeloid leukemia in first relapse after complete remission by standard induction chemotherapy. Methods Eighty - nine cases of AML in first relapse after complete remission by standard DA
基金supported by grants from the National Natural Science Foundation of China(No.82200236)Basic Research and Basic Applied Research Project of Guangzhou Science and Technology Bureau(No.202201011378)Doctoral Initiation Foundation of Guangzhou Women and Children’s Medical Center(No.2020BS010).
文摘To the Editor:Thalassemia major(TM)is a prevalent public health issue in southern China,necessitating allogeneic hematopoietic stem cell transplantation(allo-HSCT)as a curative treatment.Only a small proportion of TM patients have a sibling identical donor(SID),therefore alternative donors,including human leukocyte antigen(HLA)matched unrelated donors(MUDs)and haploidentical donors(HIDs),are increasingly being adopted by transplant centers.Several centers have indicated that MUD transplantation does not differ from SID transplantation in terms of overall survival(OS)or event-free survival(EFS)in recent years,although early complications such as graft versus host disease(GVHD)are more common among MUD transplantation.
文摘Objective To investigate the association between earlyimmune reconstitution and Epstein-Barrrvirus(EBV)reactivation by analyzing changes in natural killer(NK),B,and T cells and their functional status in the peripheral blood during the early post-transplant period.Methods This study included 23 patients who underwent haplo-hematopoietic stem cell transplantation(HSCT).The immune reconstitution of NK cells,T cells,and B cells as well as the expression levels of NK and T cell exhaustion markers(PD-1,TIM-3,and CTLA-4)and cytotoxic function at 1,2,and 3 months post-transplantation were compared between patients with EBV activation(EBV+group)and those without activation(EBV-group)post-transplantation.Results EBV activation occurredinninepatients posttransplantation(EBV+group),whereas 14 patients demonstrated no activation(EBV-group).All patients with EBV activation exhibited EBV viremia,and no EBV-associateddiseasesoccurred.No significant differences in the clinical characteristicswereffound between the two ggroupsof patients.The median proportion of CD3^(+)CD8^(+)T cells in the EBV+group was significantly lower than that in the EBV-group at 1 month post-transplantation(P=0.033).The median proportion of the CD3^(-)CD16^(neg)CD56^(bri)subset in the EBV+group was significantly higher than that in the EBV-group at 2 months postransplantation(P=0.046).No significant differences in the median proportions of CD3^(-)CD19^(+)B cells were observed between the two groups at 1,2,and 3 months post-transplantation.The expression of CTLA-4 on CD3^(-)CD16^(bri)CD56^(dim)NK cells in the EBV+group was significantly higher than that in the EBV-group at 1 month post-transplantation(P=0.033).The expression of TIM-3 on CD3^(+)CD8^(+)T cells in the EBV+group was significantly higher than that in the EBV-group(P=0.009).The expression level of TIM-3 on CD3^(-)CD16^(neg)CD56^(dim)NK cells in the EBV+group was significantly lower than that in the EBV-group at 2 months post-transplantation(P=0.023).The expression levels of TIM-3 on CD3^(+)CD4^(+)T cells in the EBV+group than those in the EBV-group at 1 and 3 months post-transplantation(P=0.002,P=0.043).The median positive rate of Granzyme B expression in CD3^(+)CD8^(+)T cells and CD3^(+)CD4^(+)T cells in the EBV+group was significantly lower than that in the EBV-group at 1-month post-transplantation(P=0.033,P=0.016).The median positive rate of Granzyme B expression in the CD3^(-)CD16^(bri)CD56^(neg)cell subset in the EBV+group was higher than that in the EBV-group at 2 months post-transplantation(P=0.012).The median positive rate of Granzyme B expression in CD3^(+)CD4^(+)T cells in the EBV+group remained significantly lower than that in the EBV-ggroup at 2 months posttransplantation(P=0.049).The median positive rate of perforin expression in the CD3^(-)CD16^(bri)CD56^(dim)cell subset was significantly higher in the EBV+group than in the EBV-group at 3 months post-transplantation(P=0.003).The median positive rate of IFNexpression in CD3^(+)CD8^(+)T cells in the EBV+group was significantly lower than that in the EBV-group at 3 months post-transplantation(P=0.036).Conclusion Delayed NK cell and T lymphocyte reconstitution,high exhaustion marker expression,and weakened cytotoxic functions may be related to EBV reactivation after haploidentical HSCT.
基金supported by grants from the project(No.RDJP2022-71)Peking University People’s Hospital Scientific Research Development Funds and the CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2019-I2M-5-034).
文摘To the Editor:Patients with relapsed or refractory(R/R)acute lymphoblastic leukemia(ALL)have a poor prognosis,with a 5-year overall survival(OS)ranging from 25%to 50%,and remission induction therapy is challenging.[1]Allogeneic hematopoietic stem cell transplantation(HSCT)is the golden standard treatment for patients with R/R ALL.Before immunotherapy was introduced into clinical practice,a significant proportion of patients could not undergo HSCT because of serious adverse events from chemotherapy or the inability to achieve an acceptably deep remission.
基金supported by National Natural Science Foundation of China(No.82370215,82020108003,and 82330008)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),Jiangsu Provincial Medical Innovation Center(No.CXZX202201)Science and Technology Program of Suzhou(No.SKY2023047)。
文摘With the advances in allogeneic hematopoietic cell transplantation(allo-HCT)and supportive care,the number of allo-HCT for elderly patients has been increasing in recent years.However,the advanced donor age limits the availability of human leukocyte antigen(HLA)-matched sibling donors(MSD)for elderly individuals.
基金supported by the National Key Research and Development Program of China(2021YFC2500300,2022YFC2502606)the Grants from the Beijing Municipal Science and Technology Commission(Z221100007422008)+4 种基金Major Program of the National Natural Science Foundation of China(82293630,82293633)CAMS Innovation Fund for Medical Sciences(2022-I2M-C&T-B-121,2023-I2MC&T-B-123)Peking University People’s Hospital Research and Development Funds(RD2023-08)Tongzhou District Distinguished Young Scholars(JCQN2023009)the Fundamental Research Funds for the Central Universities。
文摘We aimed to identify dynamic changes of lysine(K)-specific methyltransferase 2A partial tandem duplications(KMT2A-PTD)before and after haploidentical donor hematopoietic stem cell transplantation(HID HSCT)and explore the prognostic value of pre-transplantation levels of KMT2A-PTD in acute myeloid leukemia(AML)receiving HID HSCT.Consecutive 64 AML patients with KMT2A-PTD positivity at diagnosis receiving HID HSCT were included in this study.Patients with KMT2A-PTD≥1%before HSCT had a slower decrease of KMT2A-PTD after HID HSCT.Patients with KMT2A-PTD≥1%before HID HSCT had a higher cumulative incidence of relapse(36.4%,95%confidence interval[CI]:6.3%-66.5%)at 2 years after HSCT than those with KMT2A-PTD<1%(7.5%,95%CI:0.3%-14.7%,P=.010).In multivariable analysis,KMT2A-PTD≥1%before HID HSCT was the only independent risk factor for relapse(hazard ratio[HR]:4.90;95%CI:1.22-19.59;P=.025).Thus,pre-transplantation levels of KMT2A-PTD could predict relapse in AML patients following HID HSCT.
文摘Since 1968 when the first successful hematopoietic stem cell transplantation(HSCT) was performed, transplant technique has developed rapidly for more than 50 years. In the past 20 years, the significant breakthroughs and widely use of haploidentical-related donor HSCT(e.g. Beijing Protocol) make everyone can have a donor(1), and the novel, reduced-toxicity transplant regimens help elderly patients receive HSCT safely(2).
基金the National Natural Science Foundation of China (Nos.81873445, 81470342, and 81670168)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (No.81621001)the Key Program of the National Natural Science Foundation of China (Nos.81530046 and 81230013).
文摘Human leukocyte antigen (HLA)-matched donors for hematopoietic stem cell transplantation (HSCT) have long been scarce in China. Haploidentical (haplo) donors are available for the vast majority of patients, but toxicity has limited this approach. Three new approaches for haplo-HSCT originated from Italy, China, and USA in 1990 and have been developed to world-renowned system up to now. The Chinese approach have been greatly improved by implementing new individualized conditioning regimens, donor selection based on non-HLA systems, risk-directed strategies for graft-versus-host disease and relapse, and infection management. Haplo-HSCT has exhibited similar efficacy to HLA-matched HSCT and has gradually become the predominant donor source and the first alternative donor choice for allo-HSCT in China. Registry-based analyses and multicenter studies adhering to international standards facilitated the transformation of the unique Chinese experience into an inspiration for the refinement of global practice.This review will focus on how the new era in which "everyone has a donor" will become a reality in China.
基金supported by the National Key Research and Development Program of China(2019YFC0840606)from the Ministry of Science and Technologythe National Natural Science Foundation of China(82070189,81770189,81621001,and 81530046)+1 种基金the Science and Technology Project of Guangdong Province of China(2016B030230003)the Project of Health Collaborative Innovation of Guangzhou City(201704020214)。
文摘Given that randomized studies testing the long-term impact of antithymocyte globulin(ATG)dosing are scarce,we report the results of an extended follow-up from the original trial.In our prospective,multicenter,randomized trial,408 leukemia patients 14–65 years of age who underwent haploidentical hematopoietic cell transplantation(haplo-HCT)under our original“Beijing Protocol”were randomly assigned one-to-one to ATG doses of 7.5 mg/kg(n=203,ATG-7.5)or 10 mg/kg(n=205,ATG-10.0)at four sites.Extended follow-up(median 1968 d(range:1300–2710 d)indicated comparable 5-year probabilities of moderate-to-severe chronic graft-versus-host disease(GVHD)(hazard ratio(HR):1.384,95%confidence interval(CI):0.876–2.189,P=0.164),nonrelapse mortality(HR:0.814,95%CI:0.526–1.261,P=0.357),relapse(HR:1.521,95%CI:0.919–2.518,P=0.103),disease-free survival(HR:1.074,95%CI:0.783–1.473,P=0.658),and GVHD-free/relapse-free survival(HR:1.186,95%CI:0.904–1.555,P=0.219)between groups(ATG-7.5 vs.ATG-10.0).The 5-year rate of late effects did not differ significantly.However,the cytomegalovirus/Epstein-Barr virus-related death rate was much higher in the ATG-10.0 cohort than in the ATG-7.5 cohort(9.8%vs.1.5%;P=0.003).In summary,patients undergoing haplo-HCT benefit from 7.5 mg/kg ATG compared to 10.0 mg/kg ATG based on a balance between GVHD and infection control.ATG(7.5 mg/kg)is potentially regarded as the standard regimen in the platform.These results support the optimization of ATG use in the“Beijing Protocol”,especially considering the potential economic advantage in developing countries.
基金supported by the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)the National Natural Science Foundation of China(82100227)+1 种基金the Key Program of National Natural Science Foundation of China(81930004)the National Key Research and Development Program of China(2017YFA0104500)。
文摘In recent decades,haploidentical stem cell transplantation(haplo-SCT)to treat severe aplastic anemia(SAA)has achieved remarkable progress.However,long-term results are still lacking.We conducted a multicenter prospective study involving SAA patients who underwent haplo-SCT as salvage therapy.Long-term outcomes were assessed,mainly focusing on survival and quality of life(QoL).Longitudinal QoL was prospectively evaluated during pretransplantation and at 3 and 5 years posttransplantation using the SF-36 scale in adults and the PedsQL 4.0 scale in children.A total of 287 SAA patients were enrolled,and the median follow-up was 4.56 years(range,3.01–9.05 years)among surviving patients.During the long-term follow-up,268 of 275 evaluable patients(97.5%)obtained sustained full donor chimerism,and 93.4%had complete hematopoietic recovery.The estimated overall survival and failure-free survival for the whole cohort at 9 years were 85.4%±2.1%and 84.0%±2.2%,respectively.Age(≥18 years)and a poorer performance status(ECOG>1)were identified as risk factors for survival outcomes.For Qo L recovery after haplo-SCT,we found that QoL progressively improved from pretransplantation to the 3-year and 5-year time points with statistical significance.The occurrence of chronic graft versus host disease was a risk factor predicting poorer QoL scores in both the child and adult cohorts.At the last followup,74.0%of children and 72.9%of adults returned to normal school or work.These inspiring long-term outcomes suggest that salvage transplantation with haploidentical donors can be routine practice for SAA patients without human leukocyte antigen(HLA)-matched donors.
基金supported by the Beijing Talents Fund(2015000021223ZK39)the Capital’s Funds for Health Improvement and Research(2018-4-4089)+3 种基金the Key Program of the National Natural Science Foundation of China(81530046)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)the Science and Technology Project of Guangdong Province of China(2016B030230003)the Project of Health Collaborative Innovation of Guangzhou city(201704020214)
文摘A key issue in the haploiedntical hematopoietic stem cell transplantation(haplo-HSCT) setting is the search for the best donor, because donor selection can significantly impact the clinical outcomes. We aimed to identify the role of collateral related donors(CRDs) in donor selection for haplo-HSCT through comparing the clinical outcomes between CRDs(n = 60) and maternal donors(MDs, n = 296), which were the last choice of donor selection in immediate related donors(IRDs). The cumulative incidence of graft-versus-host disease was comparable between CRDs and MDs. The 5-year cumulative incidence of relapse and non-relapse mortality was 22.0%(95% CI, 11.3%–32.7%) versus 17.4%(95% CI, 13.0%–21.8%)(P = 0.455) and 25.0%(95% CI, 13.9%–36.1%) versus 23.1%(95% CI, 18.2%–28.0%)(P = 0.721) for the CRDs and MDs, respectively. The 5-year probabilities of disease-free survival and overall survival was 53.2%(95% CI, 40.4%–66.0%) versus 59.5%(95% CI, 53.8%–65.2%)(P = 0.406) and 56.5%(95% CI,43.8%–69.2%) versus 61.8%(95% CI, 56.1%–67.5%)(P = 0.458) for the CRDs and MDs, respectively.Female donor/male recipient(FDMR) CRDs were associated with the poorest clinical outcomes, and the clinical outcomes of non-FDMR CRDs were comparable to those of MDs. In summary, our results showed that CRDs did not showed superiority over MDs. Thus, IRDs should be the first choice of donor selection, and CRDs could only be the donors for those without IRDs.
